A growing wealth of data indicates that targeted therapies can mobilize a patient's own immune system to destroy malignancies with fewer side effects than traditional chemotherapy. Since it is estimated that 41% of Americans—almost 1 in 2 people—born in 2011 will develop cancer in their lifetime, the generation of more effective cancer immunotherapies is a high priority. These therapies include monoclonal antibodies (mAbs) that direct innate immune cells to tumor-associated antigens (TAA) as well as cancer “vaccines” that take many forms (including injections of tumor proteins with adjuvants or ex vivo primed dendritic cells) and are designed with the intention of inducing long-lasting anti-tumor T-cells.
The objective of the present inventors' research is to develop novel compounds capable of stimulating immune responses against tumors. The introduction of monoclonal antibodies (mAbs) has revolutionized the field of immunotherapy, particularly cancer therapy. Although mAbs have become a mainstay of cancer therapeutics, they possess serious drawbacks.1 mAbs are limited by their dangerous immunological side-reactions, lack of oral bioavailability, and high cost of production and administration. Development of synthetic molecules that mimic antibody function may provide an effective solution for the aforementioned problems.
Current research is exploring the development of new therapeutics that take advantage of the immune system's natural responses. Optimization of the Fc region of unconjugated monoclonal antibodies to increase their efficacy and response, has been of great interest.2 3 One recently developed derivative of monoclonal antibodies, bispecific antibodies, ligates two Fabs with different target specificity. One Fab region binds to the target protein of interest and the other binds to an immune receptor of choice4,5, including FcγRI6, e.g., bispecific antibodies targeting HER2 and FcγRI.6 In an alternative approach, the present inventors, and others, have utilized rational design to construct synthetic systems capable of performing, or templating, complex immunological functions.7 
As a result, several antibody-recruiting molecules (ARMs) that can modulate the immune system8 have occurred. ARMs are bifunctional synthetic molecules that contain a target-binding terminus (TBT), which binds to pathogenic surface proteins with high affinity and specificity, and an antibody-binding terminus (ABT) that recruits endogenous antibodies. We have shown that these molecules are capable of eliciting a targeted immune response selectively against both cancer and virus infected cells. This topic has been reviewed recently.4 
Notwithstanding the development of ARMs, the manipulation of the immune system with fully synthetic molecules is currently in its infancy.9 In the present invention, a relatively small molecular weight antibody mimic can perform both targeting and immune effector functions, an approach which holds greater promise for the treatment of cancer, especially prostate cancer. For the development of this fully synthetic antibody mimetic, we chose prostate cancer as our pathogenic target, although the approach can be used anywhere PSMA is expressed, including virtually all cancers, but especially prostate cancer and metastatic prostate cancer.
The choice of prostate cancer as a target for the development of the present invention reflects its severity in causing disease and death. Prostate cancer is the second leading cause of cancer related deaths among American males, and current strategies for treatment often leads to relapse and undesirable side effects.10 It has been predicted that one out of every six American men will develop prostate cancer during their lifetime. Currently, there are no clinically approved monoclonal antibody-based drugs targeting prostate cancer. Obviously, an immunological approach to the treatment of prostate cancer represents an approach with great potential, however, the negative attributes of the present immunological approaches must be ameliorated for this general approach to be successful. The present invention represents an alternative approach to address these problems.